Sensitizing multidrug-resistant leukemia cells to common cytostatics by an aluminium-salen complex that has high-apoptotic effects in leukemia, lymphoma and mamma carcinoma cells.

Abstract

We investigated the aluminium-salen complex MBR-8 as a potential anti-cancer agent. To see apoptotic effects induced by MBR-8, alone and in combination with common cytostatic drugs, DNA-fragmentations were studied using the flow cytometric analysis. Western blot analysis and measurement of the mitochondrial membrane potential with a JC-1 dye were employed to identify the pathway of apoptosis. An impressive overcoming of multidrug-resistance in leukemia (Nalm6) cells was observed. Additionally, solid tumor cells including Burkitt-like lymphoma (BJAB) and mamma carcinoma cells (MCF-7) are affected by MBR-8 in the same way. Western blot analysis revealed activation of caspase-3. MBR-8 showed very pronounced selectivity with regard to tumor cells and high synergistic effects in Nalm6 and daunorubicin-resistant Nalm6 cells when administered in combination with vincristine, daunorubicin and doxorubicin. The aluminium-salen complex MBR-8 showed very promising anti-cancer properties which warrant further development towards a cytostatic agent for future chemotherapy. Studies on aluminium compounds for cancer therapy are rare, and our report adds to this important body of knowledge.